The EVerT2 (Effective Verruca Treatments 2) trial: a randomized controlled trial of needling vs. nonsurgical debridement for the treatment of plantar verrucae.

BACKGROUND: Verrucae are a common foot skin pathology, which can in some cases persist for many years. Plantar verrucae can be unsightly and painful. There are a range of treatment options including needling. OBJECTIVES: The EVerT2 (Effective Verruca Treatments 2) trial aimed to evaluate the clinical and cost-effectiveness of the needling procedure for the treatment of plantar verrucae, relative to callus debridement. METHODS: This single-centre randomized controlled trial recruited 60 participants (aged ≥ 18 years with a plantar verruca). Participants were randomized 1 : 1 to the intervention group (needling) or the control group (debridement of the overlying callus). The primary outcome was clearance of the index verruca at 12 weeks after randomization. Secondary outcomes included recurrence of the verruca, clearance of all verrucae, number of verrucae, size of the index verruca, pain and participant satisfaction at 12 and 24 weeks. A cost-effectiveness analysis was carried out from the National Health Service perspective over 12 weeks. RESULTS: Sixty eligible patients were randomized (needling group n = 29, 48%; debridement group n = 31, 52%) and 53 were included in the primary analysis (needling n = 28, 97%; debridement n = 25, 81%). Clearance of the index verruca occurred in eight (15%) participants (needling n = 4, 14%; debridement n = 4, 16%; P = 0·86). The needling intervention costs were on average £14·33 (95% confidence interval 5·32-23·35) more per patient than for debridement. CONCLUSIONS: There is no evidence that the needling technique is more clinically or cost-effective than callus debridement. The results show a significant improvement in pain outcomes after needling compared with the debridement treatment alone.

In vitro degradation of the inner root sheath in human hair follicles lacking sebaceous glands.

BACKGROUND: Cultured hair follicles lacking sebaceous glands do not appear to degrade the inner root sheath (IRS), suggesting that the gland may be involved in this process. OBJECTIVES: To examine this supposition in cultured hair follicles. METHODS: Pilosebaceous units were isolated from hair follicles cultured in vitro, and IRS degradation was studied by histology. RESULTS: When grown in culture, the fibres of follicles lacking sebaceous glands were encased in a layer of translucent tissue. During hair growth in vitro this tissue remained intact at the distal end of the follicle but disappeared further down towards the bulb and then reappeared towards the proximal end. Transection within the region lacking this tissue resulted in the release of a naked hair fibre and the production of hair with no attached tissue upon subsequent hair growth. The translucent tissue represented the IRS, thereby demonstrating that this tissue is indeed degraded in vitro. Histological comparison with freshly isolated pilosebaceous units indicated that IRS degradation in vitro strongly resembled the process that occurs in vivo. CONCLUSIONS: These data suggest that the sebaceous gland does not itself participate in IRS degradation. Indeed, this phenomenon appears to be a function of the follicle itself and is probably intimately linked with the processes of cellular proliferation, differentiation and death that occur during hair biogenesis.

Surgical blepharoptosis--the bridle suture factor?

AIMS: To evaluate the role of the superior rectus bridle suture in the development of post cataract blepharoptosis. METHODS: We compared the incidence of postoperative ptosis in two groups of patients undergoing cataract extraction. In the first group (32 patients), a temporal corneal approach was employed with no superior rectus bridle suture. In the second group (38 patients), a superior approach with a bridle suture was used. Both groups of patients underwent phacoemulsification with the use of peribulbar anaesthesia, a pressure lowering device and a speculum. We recorded the lid position at least 12 weeks following surgery and determined the degree of postoperative ptosis. Two-sided Fischer's Exact Test was used to test for significant difference between the two groups (using a statistical software package Instat Version 3.0 for Windows). RESULTS: Taking 2 mm of ptosis as a significant change, 11.5% of those undergoing temporal section sustained postoperative ptosis whilst it occurred in 12.9% of those who underwent a superior approach. CONCLUSIONS: The presence or absence of the superior rectus bridle suture and the site of the ocular wound do not significantly contribute to the incidence of postoperative ptosis. We would suggest that the causative factors are peribulbar anaesthesia, a pressure lowering device and the use of the speculum.

Transparent thin-film TiO2 photocatalysts with high activity.

A transparent, thin-film TiO2 layer prepared by sol-gel deposition is shown to be more active for photocatalytic oxidation (PCO) of acetaldehyde, acetic acid, and toluene than Degussa P25 thin films. The sol-gel TiO2 adsorbs 30-70% less organic, but the PCO activity per adsorbed molecule is 3.5-8.5 times higher on the sol-gel TiO2 than on Degussa P25. In addition, less-reactive intermediates do not appear to form as readily on the sol-gel catalyst as they do on Degussa P25, and thus the sol-gel catalyst deactivates slower during toluene PCO. Rates were measured in transient experiments for a monolayer of adsorbed organic, and transient experiments are shown to be an effective way to measure rates, selectivities, surface coverages, and formation of less-reactive intermediates in the same set of experiments.

Telepathology between Richmond and Beckley Veterans Affairs Hospitals: report on the first 1000 cases.

OBJECTIVE: A telepathology connection between Richmond VAMC and Beckley VAMC using dynamic robotic telepathology to provide pathology services remotely was established. MATERIALS AND METHODS: This study reports a 14-month experience using telepathology to diagnose surgical specimens obtained from patients at the Beckley VA Medical Center and viewed in Richmond 250 miles away. Over 14 months, 2325 slides representing 1000 cases were viewed. RESULTS: Discrepancies were observed in 20 of 2325 slides, or 0.86% of the total. None of the patients, where a discrepancy was found, were adversely affected by the preliminary report given. CONCLUSIONS: This study demonstrates that telepathology is a reliable and cost-effective alternative to on-site pathology services and reviews advantages and disadvantages of the system.

Characterization of LHTric-1, a new monospecific monoclonal antibody to the trichocyte keratin Ha1.

The hair follicle is a heterogeneous tissue involving differentiation of both hair forming (trichocyte) and non-hair forming (root sheath) cells; while there are many antibody markers available which can determine the distribution of 'soft' epithelial keratins, fewer have been described which are truly monospecific for hair specific 'hard' keratins. We employed the proven strategy of raising monoclonal antibodies to a short synthetic peptide from the carboxy-terminal sequence of mouse Ha1 and report here the successful production of a monospecific monoclonal antibody which we have called LHTric-1. We have characterized the antibody using immunostaining on rat and human tissues and by immunoblotting against an extract of human follicles. The antibody cross-reacted between rat and human tissue but did not stain formalin-fixed tissue. LHTric-1 localized very specifically to the pre-cortical region of the hair follicle in early anagen and to pre-cortical cells in the upper bulb in anagen. Telogen follicles did not react. LHTric-1 immunoreacted within tongue and nail, staining being restricted to the mid-line above the connective tissue core in tongue and to the suprabasal layers of the nail matrix. The antibody did not react with the fully keratinized hair or nail plate. Finally, in immunoblotting, LHTric-1 reacted with a single band of 44 kDa, suggesting that a single protein was recognized. We conclude that this antibody, by virtue of its known antigen sequence specificity, will be useful in research into the formation of hair and nail in normal and diseased states.

Computing marginal expectations for large compartmentalized models with application to AIDS evolution in a prison system.

The customary models for the AIDS epidemic are compartmentalized according to criteria such as risk factors, sexual habits, gender, race, age, and HIV status and stage. Hitherto, with very few exceptions, investigators have resorted to deterministic approximations or to simulation for the computational investigation of such models, which do not yield to purely analytic methods. The present paper describes a numerical technique, not dependent on Monte Carlo simulations, for such compartmentalized Markov population processes. Analytic error bounds and computational evidence suggest that this technique is quite accurate. The study is motivated and illustrated by a model for a prison system, with ten interrelated prisons, twenty compartments, and thousands of individuals. This model is of increasing interest in itself because the HIV/AIDS epidemic is particularly virulent among prison populations, where the environment offers special opportunities to investigate various prevention and educational programmes quantitatively. Our computational techniques are shown to be effective for the analysis of such a prison system, even though the resulting Markov process is an order of magnitude more complicated than other stochastic epidemic models currently being investigated. The modelling approach and numerical device appear to be applicable to a wide variety of population processes involving migration between population patches.

Polyclonal origin of mouse skin papillomas.

We show that, from the earliest morphologically recognisable stages of development, mouse skin papillomas induced by a chemical initiation-promotion regime are polyclonal. We have demonstrated polyclonality directly by immunohistochemical staining of the mosaic cell populations in embryo aggregation chimaeras, a method which removes some of the uncertainties of previous conclusions based on analysis using electrophoretic polymorphisms. The findings may imply that initiation within a single cell and promotion of its clonal descendents is not a sufficient explanation for the origin of these tumours and that interaction between cells of more than one clone is involved.

A clonal marker induced by mutation in mouse intestinal epithelium.

A cellular marker for individual somatic cells and their clonal descendents would be a valuable tool for the investigation of cell lineages and clonal organization in developing and in renewing tissues. Such markers have been developed in Drosophila, but (apart from mutant melanocytes in retinal pigmented epithelium) not so far in mammalian tissues. We report here the development of a mutation-induced marker in mice heterozygous at the Dlb-1 locus which determines the expression of binding sites for the lectin Dolichos biflorus agglutinin (DBA) in intestinal epithelium. We show that this marker can be used to study the clonal organization of adult intestinal epithelium, and to mark descendent clones arising during development. The method can in principle be extended to any other suitable markers which can be obtained in a heterozygous state, including markers generated in transgenic animals.

Immunochemical demonstration of the clonal organization of chimaeric mouse epidermis.

The clonal organization of chimaeric mouse epidermis was demonstrated by in situ staining of whole-mount preparations using monoclonal antibodies directed against H-2k and H-2b antigens. A striking pattern of transversely oriented stripes or patches was found which extended from mid-dorsum to the flank region. The orientation of these patches indicates a preferred directional expansion of clones during the development of dorsal/lateral epidermis. The clonal pattern of the belly region differed in that stripes were not found, but a marked ventral midline boundary was observed. This demarcation line may be due to a physical effect, i.e. isolation of the left and right ventral halves of the epidermis during early embryogenesis with relatively little cell mingling following closure of the abdominal wall. The obvious nonhomogenous distribution of chimaeric components in dorsal/lateral and ventral epidermis contradicts assumptions of homogenous, fine-grained patchiness derived from electrophoretic analysis of tissue samples and used in studies of skin carcinogenesis. The observation that hair follicles may contain cells of both parental genotypes implies a polyclonal origin. Epidermal proliferative units as described by Potten (1974) were not revealed by the pattern of mosaicism at the cellular level in these chimaeric tissue sheets. This indicates that the proliferative compartment of each putative epidermal unit is polyclonal.

A study of histochemical changes in mucus from patients with ulcerative colitis, Crohn's disease, and diverticular disease of the colon.

The colonic mucosa produces a protective and lubricating layer of mucus. In certain conditions, the quantity and quality of this mucus is impaired. This study assessed the histochemical changes in mucus in inflammatory bowel disease compared with the severity and extent of the condition. Biopsy specimens were taken from 62 patients (32 with ulcerative colitis; ten with colonic Crohn's disease; ten with diverticular disease; ten with normal controls) and sections stained with high iron diamine-alcian blue to distinguish sulphated mucins from sialomucins. Normal subjects showed a predominance of sulphated mucins. The patients with Crohn's and diverticular disease also demonstrated this normal pattern. Of the 20 patients with ulcerative colitis, and without demonstrable dysplastic changes, only one showed a moderate increase in sialomucins. However, of the 12 patients with extensive colitis and dysplastic changes, ten had an increase in sialomucins. Thus, the predominant sialomucin pattern was seen mainly in patients with dysplasia. It may, therefore, indicate patients at high risk of malignancy.

Study of the histochemical changes in mucus from normal and tumour bearing mucosa in patients with colorectal cancer.

The prognosis in colorectal cancer is related to the stage of the tumour. Thus, early detection of developing tumours will significantly improve the overall prognosis. This study assessed the histochemical changes in mucus from normal and tumour bearing mucosa to determine possible premalignant changes. Eighty patients with colorectal cancer and ten normal subjects were studied. Biopsies were taken from the tumour and from adjacent 'normal' mucosa and from both resection edges. Sections were stained with high iron diamine-alcian blue to distinguish sulphated from sialomucins. All normal mucosal biopsies showed a predominantly sulphated mucin pattern. By contrast, all 70 tumour mucosal biopsies showed a marked sialomucin staining. In transitional mucosa adjacent to the tumour, 30 patients showed marked increase in sialomucin (2+), 42 a moderate increase (+) and the remaining eight a normal pattern (-ve). Twenty-one (15%) patients had increased sialomucin at either surgical resection margins, all of whom had similar changes adjacent to the tumour, suggesting a wide field change in the mucus pattern. Since these changes in mucus are associated with malignant transformation then estimation of mucus pattern may give early prediction of malignant change in patients at risk of developing primary or recurrent carcinoma.

Reduction in the stearic to oleic acid ratio in the circulating red blood cells: a possible tumour marker in solid human neoplasms.

Gas liquid chromatography study of the 18 carbon chain length fatty acids (C18FA) of the human red blood cells (RBCs) was performed on 65 patients with various clinical disorders. It was found that the stearic to oleic acid ratio (SI) of the RBCs was significantly lower (P less than 0.001) in patients with malignant conditions (n = 20, SI = 0.62 +/- 0.16) compared with pathological non-malignant diseases (n = 10, SI = 1.19 +/- 0.2) and the normal control group (n = 35, SI = 1.57 +/- 0.5). Our early results suggest that the increased unsaturation (oleic acid) in the circulating RBCs could be used as a chemical marker in various solid neoplasms.

A histochemical method that predicts local recurrence after curative resection in carcinoma of the colon and rectum.

In an attempt to develop a method to predict local recurrence that may occur following radical resection for cure in patients with carcinoma of the colon and rectum, we have studied retrospectively the histochemical characteristics of mucins in 48 surgically resected specimens. This differential pattern of mucus production at the resection margin distinguished between the patients who had local recurrence develop and those who remained tumor free.

Enkephalin-like immunoreactivity in human adrenal medullary cultures.

Normal adult human chromaffin cells in culture contain abundant immunoreactive enkephalin and exhibit spontaneous and nerve growth factor-induced outgrowth of processes. In cultures of adrenals from two age-matched white males, approximately 70 per cent of chromaffin cells from one case and 50 per cent from the other contained immunocytochemically demonstrable leuenkephalin-like material. There was no apparent correlation between enkephalin-like immunoreactivity and capacity for process outgrowth. Cells with and without processes stained for enkephalin, and the percentages of stained cells with processes appeared to change in proportion of overall process outgrowth. Numerous cells with and without processes also failed to stain for enkephalin. Marked variations in sizes of stained cells and in distribution and intensity of staining were observed in all of the cultures. These findings suggest that adult chromaffin cells are heterogeneous at a number of levels.

Leu-enkephalin-like immunoreactivity in proliferative lesions of the human adrenal medulla and extra-adrenal paraganglia.

Leu-enkephalin, a potent, endogenous, opiate-like regulatory peptide, is present in a subpopulation of normal adrenal medullary cells and in a spectrum of proliferative lesions of adrenal and extra-adrenal chromaffin cell origin. The presence, extent, and intensity of leu-enkephalin-like immunoreactivity is variable in normal and pathological states. While areas of diffuse medullary hyperplasia consistently exhibited leu-enkephalin-like immunoreactivity, approximately 50% of hyperplastic medullary nodules, pheochromocytomas, and paragangliomas were positively stained. Tumors of neuroblastic origin, on the other hand, did not contain leu-enkephalin-like immunoreactivity. Variations in leu-enkephalin-like immunoreactivity may be related to aberrations of feedback mechanisms, multicentric origins of lesions from chromaffin cells with or without the capacity for leu-enkephalin synthesis, or to a variety of other mechanisms, including defective innervation of hyperplastic and neoplastic chromaffin cells. The results of these studies indicate that leu-enkephalin-like immunoreactivity is a useful tissue marker for the demonstration of chromaffin cell hyperplasia and neoplasia and may also prove to be an important clinical marker for the assessment of chromaffin cell hyperfunction.